Older Dads Hand More DNA Changes to Kids, Research Shows

Aug. 23 (Bloomberg) -- Children of older fathers are known
to be more at risk for diseases including schizophrenia and
autism. Now, a new scientific look at the genes passed down
within families may have pinpointed a reason why.

The study, reported yesterday in the journal Nature, found
that older fathers transmit more new DNA variations to their
children than younger dads, with each added year of age
resulting in an average of 2 extra new mutations. The genetic
changes occur in men as they age because of environmental
factors, such as radiation, or through mistakes that occur in
cell division.

The research led by scientists at Reykjavik, Iceland-based
deCode Genetics Inc., is the first to quantify the number of
new, or de novo, mutations that fathers hand along by age to
their children. The findings may suggest that dads-to-be should
consider collecting their sperm at a young age and storing it
for later use, according to Alexey Kondrashov, a professor of
evolutionary biology at the University of Michigan in Ann Arbor.

“If the paternal-age effect on the de novo mutation rate
does lead to substantially impaired health in the children of
older fathers, then collecting the sperm of young adult men and
cold-storing it for later use could be a wise individual
decision,” Kondrashov wrote in an accompanying editorial that
called for further study on the issue.

Mental processes may be most affected, leading to illnesses
such as schizophrenia, because more genes express themselves in
the human brain than elsewhere.

Autism Increase

The de novo findings suggest it may be “reasonable to
assume that the ongoing increase in the incidence and prevalence
of autism in many human populations could be due, at least in
part, to the accumulation of mutations resulting from relaxed
selection and a higher average paternal age -- and not only to
better recognition of cases,” Kondrashov said.

The U.S. Centers for Disease Control and Prevention in
March reported that one in 88 children in the U.S. had autism or
a related disorder in 2008, the latest period for which data was
available. That was a 23 percent rise from 2006, the agency’s
researchers reported, saying it was unclear how much of the
increase was due to increased awareness of the disease.

Genes are the blueprints for making all the proteins needed
by the human body to grow, develop and work properly. DeCode
Genetics’ group looked at the DNA shared by 78 groups of
Icelandic mothers, fathers, and children.

A 20-year-old father transmits on average 25 new mutations
to his child while a 40-year-old transmits 65, the study found.
Mothers always transmit about 15 new mutations, regardless of
their age, according to the accompanying editorial.

Men Worse

Men probably contribute more mutations because sperm have
to divide many more times than eggs, which don’t actively split
when women are of reproductive age, according to Kondrashov.

“The only important thing when it came to explaining the
mutations was the age of the father,” said study author Kari
Stefansson, who is also the chief executive officer of deCode
Genetics. “There’s very little else to be accounted for. That’s
a stunning observation.”

Most de novo mutations are neutral, and all mutations in
the genome were once de novo, Stefansson said by telephone. Once
scientists determine the importance of de novo mutations
relative to heredity mutations in autism, it will be easy to see
how much contribution a father’s age has to the child’s health.
That work hasn’t yet been done, he said.